This parasite may really be in your head

Americans often associate parasite infections with poorly resourced communities in underdeveloped countries. But some parasites are not uncommon in the U.S.

Toxoplasma is one which many Americans may not hear about until a prenatal visit—even though over 60 million people in the U.S. are infected. The usually mild indications of infection are generally not recognized as “symptoms,” and for healthy individuals, the parasite usually retreats into self-enclosed cysts in the brain, eye, or muscles.

But for those with weak or underdeveloped immune systems—like those with cancer, HIV, or especially a fetus—Toxoplasma is quite dangerous. In a fetus unwittingly exposed via its apparently healthy mother, the infection can cause death, loss of sight, or severe neurologic deficits.

Vulnerability usually arises when the mother is exposed to Toxoplasma for the first time during her pregnancy, before her body can generate the immune response to sequester the parasite into cysts. Pregnant women are thus advised not to handle or eat raw or undercooked meat, seafood, or milk and to avoid exposure to material potentially contaminated with cat feces, including soil. Of all the many animals that can be infected with Toxoplasma, members of the cat family are the only ones in which the parasite reproduce sexually, and kittens are the most likely to excrete active parasites.

Left: a form of toxoplasmosis-causing parasite that can be transmitted through the placenta to a fetus. Right: Toxoplasma parasites (green) inside a cyst. (Rima McLeod/University of Chicago)

Rima McLeod, MD, medical director of the University of Chicago Medicine Toxoplasmosis Center and a professor of both ophthalmology and pediatrics, has spent a good part of a very active career on these one-celled animals. She and the international teams with whom she works—many of which she leads—have looked at Toxoplasma from a variety of angles: its epidemiology (Are fathers of babies with the infection likely to have it? Yes.), new animal models (Zebra fish, with their short lifespans and transparent bodies, are proving helpful for drug testing), diagnosis, treatment, and very importantly, vaccines.

Diagnosis

In France and Austria, where prenatal screening for Toxoplasma is the law, symptomatic disease has been nearly eliminated. One of McLeod’s research teams recently made a strong economic case for using an inexpensive, point-of-care diagnostic test, developed and approved in France, for all pregnant women, not only in the U.S., but in low- and middle-income countries as well. They found this simple immunological test 100 percent sensitive and specific. The cost factor is especially critical, as the test should be repeated monthly over the course of pregnancy, to identify any potential exposures while the baby is developing—the worst possible time to come in contact with these tiny animals. Babies infected with active Toxoplasma can then be treated effectively.

Unfortunately, Toxoplasma cysts, commonly located in the muscles, eyes, or brains, are usually permanent—so far, nothing can reliably eradicate them. This leaves anyone who carries the cysts—babies or adults—vulnerable to attacks from escaping parasites when immunity is low—think cancer, HIV, malnutrition, treatments for autoimmune disease.

Finding effective drug treatments that work on the cysts is therefore a priority, and McLeod and colleagues have identified a small molecule that inhibits both the parasite’s dormant and active phases—a molecule which also appears to have significant relevance in attacking the malaria parasite. A child dies of malaria every eleven seconds, with up to half a million children lost every year, so synthesizing this molecule into a viable drug could improve or save billions of lives. McLeod is now working with the Polsky Center for Entrepreneurship and Innovation to get their help in developing a safe, effective oral medicine that protects against both diseases.

A Vaccine—or Several—on the Way

McLeod and her many collaborators are advancing several vaccination strategies. One approach is to vaccinate cats so they don’t shed the parasite, which will prevent environmental contamination with Toxoplasma in their hardiest, most infectious stage.

She is also leading an effort aimed at developing a human vaccine against the parasite. The self-assembling protein nanoparticle her team has designed and produced has been proven to work in mice with human genes, although there is still work to be done to assure the vaccine works in people.

A Key to Many Diseases?

Perhaps most tantalizing is McLeod’s “systems biology” research. She has been leading a large team assembled from around the world to create a comprehensive analysis of the toxoplasmosis-infected brain, from the genes that cause disease susceptibility; to the proteins those genes encode; to how these molecules affect the neural, immune, and endocrine networks; to identifying biomarkers of infection and disease.

They have found significant crossover between the biochemical pathways involved in toxoplasmosis and those in many other neurological disorders: proteins associated with the neurodegeneration in Parkinson’s and Alzheimer’s diseases, others involved with epilepsy, and still others involved in cell proliferation and cancer. Thus, deep discovery in the basic science of toxoplasmosis may offer a roadmap to understanding many neuropathologies and give clues to treat or prevent them.